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      Attenuation of Red Blood Cell Storage Lesions with Vitamin C

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          Abstract

          Stored red blood cells (RBCs) undergo oxidative stress that induces deleterious metabolic, structural, biochemical, and molecular changes collectively referred to as “storage lesions”. We hypothesized that vitamin C (VitC, reduced or oxidized) would reduce red cell storage lesions, thus prolonging their storage duration. Whole-blood-derived, leuko-reduced, SAGM (saline-adenine-glucose-mannitol)-preserved RBC concentrates were equally divided into four pediatric storage bags and the following additions made: (1) saline (saline); (2) 0.3 mmol/L reduced VitC (Lo VitC); (3) 3 mmol/L reduced VitC (Hi VitC); or (4) 0.3 mmol/L oxidized VitC (dehydroascorbic acid, DHA) as final concentrations. Biochemical and rheological parameters were serially assessed at baseline (prior to supplementation) and Days 7, 21, 42, and 56 for RBC VitC concentration, pH, osmotic fragility by mechanical fragility index, and percent hemolysis, LDH release, glutathione depletion, RBC membrane integrity by scanning electron microscopy, and Western blot for β-spectrin. VitC exposure (reduced and oxidized) significantly increased RBC antioxidant status with varying dynamics and produced trends in reduction in osmotic fragility and increases in membrane integrity. Conclusion: VitC partially protects RBC from oxidative changes during storage. Combining VitC with other antioxidants has the potential to improve long-term storage of RBC.

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          Most cited references36

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          An update on red blood cell storage lesions, as gleaned through biochemistry and omics technologies.

          Red blood cell (RBC) aging in the blood bank is characterized by the accumulation of a significant number of biochemical and morphologic alterations. Recent mass spectrometry and electron microscopy studies have provided novel insights into the molecular changes underpinning the accumulation of storage lesions to RBCs in the blood bank. Biochemical lesions include altered cation homeostasis, reprogrammed energy, and redox metabolism, which result in the impairment of enzymatic activity and progressive depletion of high-energy phosphate compounds. These factors contribute to the progressive accumulation of oxidative stress, which in turn promotes oxidative lesions to proteins (carbonylation, fragmentation, hemoglobin glycation) and lipids (peroxidation). Biochemical lesions negatively affect RBC morphology, which is marked by progressive membrane blebbing and vesiculation. These storage lesions contribute to the altered physiology of long-stored RBCs and promote the rapid clearance of up to one-fourth of long-stored RBCs from the recipient's bloodstream after 24 hours from administration. While prospective clinical evidence is accumulating, from the present review it emerges that biochemical, morphologic, and omics profiles of stored RBCs have observable changes after approximately 14 days of storage. Future studies will assess whether these in vitro observations might have clinically meaningful effects.
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            Influence of storage on red blood cell rheological properties.

            It is known that the age of transfused blood is a risk factor for the development of multiple organ failure in surgical patients. However, the character of hemorrheological changes in stored blood as well as the time when they appear remains disputable. We assumed that blood storage was accompanied by a progressive decrease of RBC deformability and rheological disorders. The degree of rheological disturbances should be directly proportional to the number of RBC with altered geometry. Nine packages of RBC kept in adenine saline solution were examined from the 5th to the 42nd day of storage. RBC deformability index (DI) was determined by micropore filtration technique. RBC shape was estimated by means of scanning electron microscopy. Blood clotting time was measured by Sonoclot coagulation analyzer. Significant alterations of RBC shape started at the second week of storage and progressed during the rest of the storage period. RBC shape changes were accompanied by progressive decrease in DI and increase in hemolysis and acidosis. The correlation index between the percentage of abnormally shaped RBC and DI was -0.81 (P = 0.0258). Blood clotting progressively decreased after 2 weeks of storage, probably due to the exhaustion of some procoagulant plasma factors. Serious hemorrheological disorders, including the decrease in RBC deformability secondary to shape abnormalities, acidosis, and the decrease of blood clotting, start already at the second week of storage and progress up to the end of the storage period. Transfusion of packed RBC older than 7 days may contribute to hemorrheological disorders in critically ill patients. (c)2002 Elsevier Science.
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              Red cell changes during storage.

              John Hess (2010)
              Red blood cells can be stored in liquid suspension in approved additive solutions for periods up to 6 weeks with 0.4% hemolysis, 84% 24-h in vivo recovery, and normal subsequent survival of the cells that persist in the circulation for at least 24h. However, while they are stored, the red cells undergo changes including the loss of adenosine triphosphate, diphosphoglycerate, and potassium, oxidative injury to proteins, lipids, and carbohydrates, loss of shape and membrane, increased adhesiveness, decreased flexibility, reduced capillary flow, and decreased oxygen delivery. Deaths have been reported related to the high potassium and lysophospholipids, but are rare. (c) 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Antioxidants (Basel)
                Antioxidants (Basel)
                antioxidants
                Antioxidants
                MDPI
                2076-3921
                12 July 2017
                September 2017
                : 6
                : 3
                : 55
                Affiliations
                [1 ]Department of Pathology, Director, Transfusion Services, Virginia Commonwealth University, Richmond, VA 23298, USA; kimberly.sanford@ 123456vcuhealth.org
                [2 ]Department of Internal Medicine, Virginia Commonwealth University, Richmond, VA 23298, USA; bernard.fisher@ 123456vcuhealth.org (B.J.F.); evan.fowler@ 123456vcuhealth.org (E.F.); alpha.fowler@ 123456vcuhealth.org (A.A.F.)
                Author notes
                [* ]Correspondence: ramesh.natarajan@ 123456vcuhealth.org ; Tel.: +1-804-827-1013
                Author information
                https://orcid.org/0000-0002-3431-9971
                Article
                antioxidants-06-00055
                10.3390/antiox6030055
                5618083
                28704937
                1cf75488-9045-4aa2-bc58-e1355085c6ba
                © 2017 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 06 June 2017
                : 08 July 2017
                Categories
                Article

                vitamin c,rbc storage lesions,mean fragility index,β-spectrin,scanning electron microscopy

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